title: Biologically active oligodeoxyribonucleotides--IX. Synthesis and anti-HIV-1 activity of hexadeoxyribonucleotides, TGGGAG, bearing 3'- and 5'-end-modification.
abstract: We have determined that hexadeoxyribonucleotides (5'TGGGAG3'), with modified aromatic groups such as a trityl group at the 5'-end, have anti-HIV-1 activity in vitro. The 6-mer bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5'-end had the most potent activity and the least cytotoxicity. When the 3'-end of the 5'-(3,4-DBB)-modified 6-mer was substituted with a 2-hydroxyethylphosphate, a 2-hydroxyethylthiophosphate, or a methylphosphate group at the 3'-end, anti-HIV-1 activity increased. Moreover, among various 3'- and 5'-end-modified 6-mers that were tested, the 6-mer (R-95288) bearing a 3,4-DBB group at the 5'-end and a 2-hydroxyethylphosphate group at the 3'-end was the most stable, when incubated with mouse, rat, or human plasma. Therefore, R-95288 was chosen as the best candidate for possible use in therapy on the basis of its anti-HIV-1 activity.
authors.affiliation: Exploratory Chemistry Research Laboratory, Sankyo Co., Ltd., Tokyo, Japan. koizum@shina.sankyo.co.jp
authors.forename: M
authors.initials: M
authors.lastname: Koizumi
authors.forename: R
authors.initials: R
authors.lastname: Koga
authors.forename: H
authors.initials: H
authors.lastname: Hotoda
authors.forename: K
authors.initials: K
authors.lastname: Momota
authors.forename: T
authors.initials: T
authors.lastname: Ohmine
authors.forename: H
authors.initials: H
authors.lastname: Furukawa
authors.forename: T
authors.initials: T
authors.lastname: Agatsuma
authors.forename: T
authors.initials: T
authors.lastname: Nishigaki
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: T
authors.initials: T
authors.lastname: Kosaka
authors.forename: S
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: J
authors.initials: J
authors.lastname: Sone
authors.forename: M
authors.initials: M
authors.lastname: Kaneko
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Shimada
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D002942:Circular Dichroism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
chemical_list: D019380:Anti-HIV Agents; D009838:Oligodeoxyribonucleotides